The Orexin receptor-2 gene (OX2R) as a candidate gene in somnolence associated with sertraline in depressed patients

Background and Aim : Selective serotonin reuptake inhibitors (SSRIs) are considered as first-line drugs for treating depressive disorders. Among the adverse effects reported with sertraline is sleep disturbances however the etiology lying beneath is obscure. Orexin the most recently discovered neurotransmitter is involved in sleep cycle. It exerts its physiological actions by means of orexin receptor 1 and 2 (OXR1 & OXR2). Dysfunction of orexin system contributes to various psychiatric, neurologic and neuropsychiatric disorders. Thus the aim of our study was to assess the possible association of genetic variation of OX2R G1246A with hypersomnia reported with sertraline in a group of MDD patients.Methods : Ninety six newly diagnosed MDD patients were enrolled in our cohort study. MDD was assessed using DSMV criteria. Sleep pattern was assessed using PSQI. Patients were interviewed at base line (week 0) and week 4. Blood samples were collected for further genotyping of OX2R G1246A by means of PCR-RFLP.Results : Results of our study indicate a strong association between G1264A polymorphism of OX2R and hypersomnia. Hypersomnia with sertraline happens by 4.6 folds (P=0.001; OR=4.67; 95%CI: 1.83-11.87) in patients having the genotype with the A allele (AA and GA genotypes). Patients with the A allele experience hypersomnia 3 folds more than carriers of the G allele (P=0.001; OR=3.16, 95%CI= 1.59-6.27).Conclusion : In conclusion, G1246A variant might be a predictor for somnolence in MDD patients treated with sertraline. Our findings support the idea that some variants of the OXRs might contribute to inter individual variability in sleep pattern of patients receiving antidepressants.

Keywords:

Orexin receptor-2 , Sleep , Hypersomnia , Selective serotonin reuptake inhibitors , Sertraline